This Project will investigate the mechanisms that controlt he trafficking of antigen-specificT-cells to sites of herpes simplex virus type2 (HSV-2) infection. The homing of memory HSV-specificT-cells to infected mucocutaneous tissuesis an important component of the host response to a mucosal infection such as HSV-2. We have made HLA class I & II tetramer reagents that permit study of the homing properties and effect orf unctions of circulating HSV-2-specific CD8+ and CD4+ T-cells. SpecificAim I defines expression of candidate skin and mucosal adhesion receptors, including cutaneous lymphocyte-associated antigen(CLA), A4B7 integrin,& AEB7 integrin,by HSV-specific T-cells during chronic infection. We will measure the expression of the skin & mucosa associated chemokine receptors CCR4, CCR6, CXCR3, & CCR10 by HSV-specificT-cells. In parallel experiments,we will assess the function of adhesion & chemokine receptors infunctional ssays, and measure the expression of these molecules and their ligands in vivo. Specific Aim 2 will define the temporal dynamics of the CD8+ T-cell response to HSV during primary infection, and compare this with the time course of CLA & chemokine receptor expression by these cells. We will monitor HSV-2 shedding rates prospectively to determine if the acquisition of CLA or other adhesion or chemokine receptors is temporally correlated with a reduction in HSV-2 shedding. The levels of expression of molecules associated with cytolytic activity,and the secretion of antiviral cytokines, will also be measured in HSV-specificT-cells. SpecificAim 3 will compare circulating HSV-2 specific CD8+ T-cells that have high and low levels of CLA expression. We hypothesize that cells expressing high levels of CLA are specialized for encounter with infected cells in the skin, & will have higher CTL & antiviral cytokine secretion, and lower lymph node-homing markers including CCR7 & CD62L, than will HSV-2-specific T-cells expressing low levels of CLA.